Modulation of tissue transglutaminase in tubular epithelial cells alters extracellular matrix levels: a potential mechanism of tissue scarring

The up-regulation and trafficking of tissue transglutaminase (TG2) by tubular epithelial cells (TEC) has been implicated in the development of kidney scarring. TG2 catalyses the crosslinking of proteins via the formation of highly stable e(?-glutamyl) lysine bonds. We have proposed that TG2 may contribute to kidney scarring by accelerating extracellular matrix (ECM) deposition and by stabilising the ECM against proteolytic decay. To investigate this, we have studied ECM metabolism in Opossum kidney (OK) TEC induced to over-express TG2 by stable transfection and in tubular cells isolated from TG2 knockout mice. Increasing the expression of TG2 led to increased extracellular TG2 activity (p < 0.05), elevated e(?-glutamyl) lysine crosslinking in the ECM and higher levels of ECM collagen per cell by 3H-proline labelling. Immunofluorescence demonstrated that this was attributable to increased collagen III and IV levels. Higher TG2 levels were associated with an accelerated collagen deposition rate and a reduced ECM breakdown by matrix metalloproteinases (MMPs). In contrast, a lack of TG2 was associated with reduced e(?-glutamyl) lysine crosslinking in the ECM, causing reduced ECM collagen levels and lower ECM per cell. We report that TG2 contributes to ECM accumulation primarily by accelerating collagen deposition, but also by altering the susceptibility of the tubular ECM to decay. These findings support a role for TG2 in the expansion of the ECM associated with kidney scarring.

Inhibition of transglutaminase activity reduces extracellular matrix accumulation induced by high glucose levels in proximal tubular epithelial cells

Diabetic nephropathy affects 30-40% of diabetics leading to end-stage kidney failure through progressive scarring and fibrosis. Previous evidence suggests that tissue transglutaminase (tTg) and its protein cross-link product epsilon(gamma-glutamyl)lysine contribute to the expanding renal tubulointerstitial and glomerular basement membranes in this disease. Using an in vitro cell culture model of renal proximal tubular epithelial cells we determined the link between elevated glucose levels with changes in expression and activity of tTg and then, by using a highly specific site directed inhibitor of tTg (1,3-dimethyl-2[(oxopropyl)thio]imidazolium), determined the contribution of tTg to glucose-induced matrix accumulation. Exposure of cells to 36 mm glucose over 96 h caused an mRNA-dependent increase in tTg activity with a 25% increase in extracellular matrix (ECM)-associated tTg and a 150% increase in ECM epsilon(gamma-glutamyl)lysine cross-linking. This was paralleled by an elevation in total deposited ECM resulting from higher levels of deposited collagen and fibronectin. These were associated with raised mRNA for collagens III, IV, and fibronectin. The specific site-directed inhibitor of tTg normalized both tTg activity and ECM-associated epsilon(gamma-glutamyl)lysine. Levels of ECM per cell returned to near control levels with non-transcriptional reductions in deposited collagen and fibronectin. No changes in transforming growth factor beta1 (expression or biological activity) occurred that could account for our observations, whereas incubation of tTg with collagen III indicated that cross-linking could directly increase the rate of collagen fibril/gel formation. We conclude that Tg inhibition reduces glucose-induced deposition of ECM proteins independently of changes in ECM and transforming growth factor beta1 synthesis thus opening up its possible application in the treatment other fibrotic and scarring diseases where tTg has been implicated.

Design optimization of short-stroke single-phase tubular permanent-magnet motor for refrigeration applications

This paper describes a design methodology to achieve optimal performance for a short-stroke single-phase tubular permanent-magnet motor which drives a reciprocating vapor compressor. The steady-state characteristic of the direct-drive linear-motor compressor system is analyzed, an analytical formula for predicting iron loss is presented, and a motor-design procedure which takes into account the effect of compressor loads under nominal operating condition is formulated. It is shown that the motor efficiency can be optimized with respect to two leading dimensional ratios. Experimental results validate the proposed design methodology. Copyright © 2010 IEEE.

ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells

Extracellular signal-regulated kinase 5 (ERK5) is activated in response to environmental stress and growth factors. Gene ablation of Erk5 in mice is embryonically lethal as a result of disruption of cardiovascular development and vascular integrity. We investigated vascular endothelial growth factor (VEGF)-mediated ERK5 activation in primary human dermal microvascular endothelial cells (HDMECs) undergoing proliferation on a gelatin matrix, and tubular morphogenesis within a collagen gel matrix. VEGF induced sustained ERK5 activation on both matrices. However, manipulation of ERK5 activity by siRNA-mediated gene silencing disrupted tubular morphogenesis without impacting proliferation. Overexpression of constitutively active MEK5 and ERK5 stimulated tubular morphogenesis in the absence of VEGF. Analysis of intracellular signalling revealed that ERK5 regulated AKT phosphorylation. On a collagen gel, ERK5 regulated VEGF-mediated phosphorylation of the pro-apoptotic protein BAD and increased expression of the anti-apoptotic protein BCL2, resulting in decreased caspase-3 activity and apoptosis suppression. Our findings suggest that ERK5 is required for AKT phosphorylation and cell survival and is crucial for endothelial cell differentiation in response to VEGF.

Tubular and sector heat pipes with interconnected branches for gas turbine and/or compressor cooling

Designing turbines for either aerospace or power production is a daunting task for any heat transfer scientist or engineer. Turbine designers are continuously pursuing better ways to convert the stored chemical energy in the fuel into useful work with maximum efficiency. Based on thermodynamic principles, one way to improve thermal efficiency is to increase the turbine inlet pressure and temperature. Generally, the inlet temperature may exceed the capabilities of standard materials for safe and long-life operation of the turbine. Next generation propulsion systems, whether for new supersonic transport or for improving existing aviation transport, will require more aggressive cooling system for many hot-gas-path components of the turbine. Heat pipe technology offers a possible cooling technique for the structures exposed to the high heat fluxes. Hence, the objective of this dissertation is to develop new radially rotating heat pipe systems that integrate multiple rotating miniature heat pipes with a common reservoir for a more effective and practical solution to turbine or compressor cooling. In this dissertation, two radially rotating miniature heat pipes and two sector heat pipes are analyzed and studied by utilizing suitable fluid flow and heat transfer modeling along with experimental tests. Analytical solutions for the film thickness and the lengthwise vapor temperature distribution for a single heat pipe are derived. Experimental tests on single radially rotating miniature heat pipes and sector heat pipes are undertaken with different important parameters and the manner in which these parameters affect heat pipe operation. Analytical and experimental studies have proven that the radially rotating miniature heat pipes have an incredibly high effective thermal conductance and an enormous heat transfer capability. Concurrently, the heat pipe has an uncomplicated structure and relatively low manufacturing costs. The heat pipe can also resist strong vibrations and is well suited for a high temperature environment. Hence, the heat pipes with a common reservoir make incorporation of heat pipes into turbo-machinery much more feasible and cost effective.

Incrustação em poço produtor de petróleo e gás natural: um estudo de caso

Water and gas is a common by - product of the oil production process. Production may be compromised by the precipitation of inorganic salts in both the reservoir and producing well, through scale formation. This precipitation is likely the cause of the formation damage. High temperatures and h igh pressures (HTHP) may favor the precipitation of insoluble salts. The most common types of scale in oil fields are calcium carbonate and calcium sulphate, strontium and barium sulphate. New types of scale formation have attracted special attention such as zinc sulphide and lead. This precipitation may occur in the pores of reservoir rocks, in the production string and in equipment, causing obstructions and consequent production losses. In this study, the influence of well depth on incrustation compositio n was investigated to design removal treatments and assess the behavior of these deposits along the string, through the analysis of pressure and temperature. Scale residues were recovered from the inside of the production string of an oil and gas well duri ng the string removal operation. A total of 10 samples from different depths (15.4 m to 4061.5 m) were obtained. Initially a dissolution test was conducted in weak acid, similar to that used in removal operations with this type of scale formation. Majority composition was defined and confirmed by dissolution tests using X - Ray Fluorescence Spectroscopy (XRF), X - Ray Diffraction (XRD) and Scanning Electron Microscope (SEM) techniques. Residues with distinct characteristics were observed in different proportion s, showing a tendency toward increased and/or decreased mass with depth. In the samples closest to the surface, typical sandstone residues were found, with calcium (45% Ca) as the metal of highest concentration. The obtained results indicate correlations o f the scale types studied with the depth and, consequently, with the thermodynamic conditions of pressure and temperature.

Território para viver: dinâmicas territoriais da comunidade quilombola de Acauã, Poço Branco, Rio Grande do Norte

In the late 1980s, the quilombola (or maroon) communities emerged on the Brazilian public scene. They established themselves as new collective subjects and ethnic groups, in a historical moment of sensitive political changes in several social conflicts and struggles, both in Brazil and in Latin America. Because of their socio-cultural and historical singularities, these communities have self-identified in the same collective expression and have organized in search of recognition and respect for their rights. Quilombo communities and other self-labeled as "traditional communities" seek to reaffirm their differences in opposition to a conscious colonizer cultural project and re-signify their memories and traditions, that serve as reference in the construction of alternative production projects and community organization. One of the distinguishing characteristics of this quilombola political emergence process is the territorial nature of the struggles, manifested in at least two directions: on the one hand, the struggle for legal and formal recognition of a given space, i.e., the regularization and titling of occupied territories, considering that the Brazilian Constitution of 1988 recognizes the right of these communities to the final possession of the traditional lands. On the other hand, the struggle for recognition of their territoriality in a broader sense, not necessarily restricted to the demarcated area, but as the recognition of a culture and its own way of life, that originated historically in these territories. The current accomplishments and challenges of the Brazilian quilombola communities are well exemplified by the quilombo of Acauã, in the Poço Branco municipality of Rio Grande do Norte. The last fifteen years have been marked by important changes in this community, which has gained visibility and has emerged as a new political player. Acauã identified itself as quilombola community in 2004, the same year that it formalized its political structure, through the creation of the Association of Residents of Quilombo Acauã (AMQA, in Portuguese). Also in 2004, it requested to the National Institute of Colonization and Land Reform (INCRA, in Portuguese) the opening of the process for regularization and titling of quilombo territory, which is at an advanced stage, but so far without definitive resolution. This study aims to understand the process of territorialization (struggle for territorial claim) played in the last fifteen years by the community of Acauã.

Resolução em tomografia de tempo de trânsito poço-a-poço: a dependência da iluminação

The key aspect limiting resolution in crosswell traveltime tomography is illumination, a well known result but not as well exemplified. Resolution in the 2D case is revisited using a simple geometric approach based on the angular aperture distribution and the Radon Transform properties. Analitically it is shown that if an interface has dips contained in the angular aperture limits in all points, it is correctly imaged in the tomogram. By inversion of synthetic data this result is confirmed and it is also evidenced that isolated artifacts might be present when the dip is near the illumination limit. In the inverse sense, however, if an interface is interpretable from a tomogram, even an aproximately horizontal interface, there is no guarantee that it corresponds to a true interface. Similarly, if a body is present in the interwell region it is diffusely imaged in the tomogram, but its interfaces - particularly vertical edges - can not be resolved and additional artifacts might be present. Again, in the inverse sense, there is no guarantee that an isolated anomaly corresponds to a true anomalous body because this anomaly can also be an artifact. Jointly, these results state the dilemma of ill-posed inverse problems: absence of guarantee of correspondence to the true distribution. The limitations due to illumination may not be solved by the use of mathematical constraints. It is shown that crosswell tomograms derived by the use of sparsity constraints, using both Discrete Cosine Transform and Daubechies bases, basically reproduces the same features seen in tomograms obtained with the classic smoothness constraint. Interpretation must be done always taking in consideration the a priori information and the particular limitations due to illumination. An example of interpreting a real data survey in this context is also presented.

Resolução em tomografia de tempo de trânsito poço-a-poço: a dependência da iluminação

The key aspect limiting resolution in crosswell traveltime tomography is illumination, a well known result but not as well exemplified. Resolution in the 2D case is revisited using a simple geometric approach based on the angular aperture distribution and the Radon Transform properties. Analitically it is shown that if an interface has dips contained in the angular aperture limits in all points, it is correctly imaged in the tomogram. By inversion of synthetic data this result is confirmed and it is also evidenced that isolated artifacts might be present when the dip is near the illumination limit. In the inverse sense, however, if an interface is interpretable from a tomogram, even an aproximately horizontal interface, there is no guarantee that it corresponds to a true interface. Similarly, if a body is present in the interwell region it is diffusely imaged in the tomogram, but its interfaces - particularly vertical edges - can not be resolved and additional artifacts might be present. Again, in the inverse sense, there is no guarantee that an isolated anomaly corresponds to a true anomalous body because this anomaly can also be an artifact. Jointly, these results state the dilemma of ill-posed inverse problems: absence of guarantee of correspondence to the true distribution. The limitations due to illumination may not be solved by the use of mathematical constraints. It is shown that crosswell tomograms derived by the use of sparsity constraints, using both Discrete Cosine Transform and Daubechies bases, basically reproduces the same features seen in tomograms obtained with the classic smoothness constraint. Interpretation must be done always taking in consideration the a priori information and the particular limitations due to illumination. An example of interpreting a real data survey in this context is also presented.

Tubular micro- and nanostructures of TCO materials grown by a vapor-solid method

Microtubes and rods with nanopipes of transparent conductive oxides (TCO), such as SnO_2, TiO_2, ZnO and In_2O_3, have been fabricated following a vapor-solid method which avoids the use of catalyst or templates. The morphology of the as-grown tubular structures varies as a function of the precursor powder and the parameters employed during the thermal treatments carried out under a controlled argon flow. These materials have been also doped with different elements of technological interest (Cr, Er, Li, Zn, Sn). Energy Dispersive X-ray Spectroscopy (EDS) measurements show that the concentration of the dopants achieved by the vapor-solid method ranges from 0.5 to _3 at.%. Luminescence of the tubes has been analyzed, with special attention paid to the influence of the dopants on their optical properties. In this work, we summarize and discuss some of the processes involved not only in the anisotropic growth of these hollow micro and nanostructures, but also in their doping.

Fabrication and evaluation of NiO/Y2O3-stabilized-ZrO2 hollow fibers for anode-supported micro-tubular solid oxide fuel cells

In this work NiO/3mol% Y₂O₃-ZrO₂ (3YSZ) and NiO/8mol% Y₂O₃-ZrO₂ (8YSZ) hollow fibers were prepared by phase-inversion. The effect of different kinds of YSZ (3YSZ and 8YSZ) on the porosity, electrical conductivity, shrinkage and flexural strength of the hollow fibers were systematically evaluated. When compared with Ni-8YSZ the porosity and shrinkage of Ni-3YSZ hollow fibers increases while the electrical conductivity decreases, while at the same time also exhibiting enhanced flexural strength. Single cells with Ni-3YSZ and Ni-8YSZ hollow fibers as the supported anode were successfully fabricated showing maximum power densities of 0.53 and 0.67Wcm^-2 at 800°C, respectively. Furthermore, in order to improve the cell performance, a Ni-8YSZ anode functional layer was added between the electrolyte and Ni-YSZ hollow fiber. Here enhanced peak power densities of 0.79 and 0.73Wcm^-2 were achieved at 800°C for single cells with Ni-3YSZ and Ni-8YSZ hollow fibers, respectively.